Microvascular abnormalities and pathologies occur in all the tissues and organs of diabetic patients. Cellular abnormalities in the microvessels extend to both vascular cells and innervation surrounding the microvasculature. We suggest that microvascular diseases in the retina and those in the skin or peripheral tissues may share many common characteristics in early stages of diabetes. Thus, imaging techniques to assess both vascular and neurological functions via the retina may be helpful to diagnose and quantitate microvascular and neurological damage in the periphery. This postulate is based on the fact that clinically, diabetic retinopathy and sensory polyneuropathy (DPN), occurs frequently together. Functional studies have shown that blood flow is decreased in the retina and peripheral nerve early in the course of diabetes. Common pathologies for both tissues include pericyte loss, basal membrane thickening, capillary dropouts and microaneurysms. Thus, imaging tests that could directly assess retinal microvascular dysfunction and sensory abnormalities in diabetic patients may also detect peripheral microvascularopathy and sensory neuropathy at earlier time since it is much easier to visualize retinal microvasculature and potentially neurological functions than the microvessels of the skin or nerves. In collaboration with Dr. Veves and Dr. Bursell, we have developed a series of retinal and systemic microvascular function tests to evaluate their possible use for the diagnosis of microvascular disease in diabetic patients. The retinal function tests are: digitalized retinal video fluorescein angiogram (VFA) for quantitating microvascular flow; retinal oximetry (RO) for measuring oxygen saturation; and electroretinogram (ERG) for measuring neural-retina functions. The results from these retinal functions will be correlated to peripheral microvascular and sensory function tests which will include neuropathy sensory score (NSS), neuropathy disability score (NDS) and quantitative sensory testing (QST) and nerve axonal reflex (NAR) for measuring sensory fiber abnormalities and skin blood flow by laser Doppler flowmetry. The specific aims for this grant are: 1) to determine in control and non-diabetic subjects from 18-35 years of age, the normal range for changes in VFA, RO and ERG and several neural vascular function tests such as NSS, NDS, QST, nerve axonal reflex and skin blood flow by laser Doppler both breathing room air and 12 percent and 100 percent oxygen (O2) in the breathing air; 2) to assess correlation between retinal, neural and microvascular changes by ERG, VFA and RO and peripheral microvascular and sensory functions as described in specific aim 1 in Type 1 diabetic patients with no or minimal retinopathy, moderate and severe non-proliferative diabetic retinopathy. These studies should provide us with information on whether retinal neural and vascular imaging function tests can be related to peripheral neural and microvascular dysfunctions and pathologies in diabetic patients.